The purpose of this project is to develop a nanoparticle-based drug delivery system for use in the treatment of the exudative form of aged-related macular degeneration (ARMD). ARMD is the leading cause of blindness for individuals over fifty-five years of age that live in the industrialized world. It affects approximately 10 million people in the US and as many as 30 million worldwide. There are two forms of the disease, both of which cause a loss of central vision. Approximately eighty-five percent of patients have the less severe dry form that produces gradual but rarely complete vision loss. The remaining fifteen percent have the severe wet, or exudative, form that causes rapid, disabling blindness. Wet ARMD is further characterized by choroidal neovascularization (CNV), a growth under the macula of abnormal blood vessels originating from the choroidal capillary bed. Research has linked chronic inflammation to both forms of ARMD. The advent of novel anti-angiogenic agents has enabled pharmaceutical treatment of ARMD but only for the wet form of the disease. These treatments are severely limited by the fact that the drug must be directly injected into the eye. This procedure carries a significant risk of complication and generates understandable issues of patient acceptability. Estimates predict that as many as one half of patients will discontinue treatment because of ocular injection. Thus, there is a clear need for a therapy that either bypasses the need for ocular injection or reduces its frequency. The chitosan-based nanoparticle delivery system we propose to develop intends to meet this need. Successful completion of this Phase I project will result in a prototype nanoparticle that can be injected intravenously and home to inflamed blood vessels in the eye and release an anti-angiogenic agent locally over a period of weeks to months. [unreadable] [unreadable] [unreadable] [unreadable]